Multipotent stem cells, cells capable of extensive growth without losing their potential for differentiating into a plurality of cell types, are found in fetal and various adult tissues. Multipotent stem cells have been isolated from fetal tissue and bone marrow.
Cell differentiation in the developing embryo is regulated by extrinsic inductive signals and an intrinsic programmed genetic code. Differentiation into the three germ layers (ectodern, endoderm, and mesoderm) from primitive ectoderm (epiblast) is a crucial step during development and previously thought to be an irreversible process leading to a germ layer giving rise to unique types of cells, e.g., epidermal or neuronal cells from ectoderm; epithelial cells in internal organs or digestive tract from endoderm; and hemopoietic and mesenchymal cells from mesoderm. Recent studies of cell transplantation, however, have indicated that somatic stem cells or progenitor cells from adult tissues and with characteristic tissue-specific markers were able, possibly, to generate cells with fates different from those heretofore recognized as descendants of a specific germ layer. Although the evidence for this is still inconclusive, if proven true it would an example of a process called “transdifferentiation” and leads to questions about possible mechanisms. A candidate example of putative transdifferentiation is that of CD45+ hemopoietic stem cells giving rise to mature hepatocytes.
Adult liver parenchymal cells consist of hepatocytes and biliary epithelial cells. They are derived from common precursors, hepatoblasts, that come from foregut endodermal stem cells by an inductive signal(s) from the septum transversum surrounding the outpouching of the endoderm. Although it is not known whether hemopoietic cells can differentiate into hepatoblasts, there does appear to be a subpopulation of progenitors in the bone marrow capable of maturing into hepatocytes and sharing critical antigenic markers with that of hemopoietic progenitors; therefore, these hemopoietic progenitor cells should express some endodermal markers before full differentiation into hepatocytes.
Alpha-fetoprotein (AFP) is a major serum protein produced primarily by endoderm-derived yolk sac and by hepatoblasts as well as more differentiated fetal hepatic cells. AFP is one of the earliest markers for endodermal differentiation; the transcriptional expression starts at visceral and definitive endoderm in the early embryo and is regulated tightly in a developmental and tissue-specific manner. Therefore, in most studies in which is assessed endodermal differentiation of human embryonic stem cells or embryonic germ cells, the expression of AFP mRNA has been investigated and used as a marker of endoderm.